parallel randomized trial

NCT04667377

A Phase II, Randomized, Double Blind, Parallel Group,46 Weeks Dose-finding Study of BI 456906 Administered Once Weekly Subcutaneously Compared With Placebo in Patients With Obesity or Overweight

Overweight or obesity without diabetes (adults)NCT04667377S002375

Design

Randomized: 387
Start year: 2021
Treatment: 46 weeks
Countries: multinational (43 sites)
Sponsor: Boehringer Ingelheim (industry)
Eligibility: age 18 to under 75; BMI 27 or more; HbA1c below 6.5 percent; weight 70 kg women or 80 kg men or more

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Survodutide 0.6 mg subcutaneous once weekly Survodutide 0.6 mg	lifestyle: standard	78	77	47
A2	Survodutide 2.4 mg subcutaneous once weekly Survodutide 2.4 mg	lifestyle: standard	78	78	45
A3	Survodutide 3.6 mg subcutaneous once weekly Survodutide 3.6 mg	lifestyle: standard	77	76	48
A4	Survodutide 4.8 mg subcutaneous once weekly Survodutide 4.8 mg	lifestyle: standard	77	76	47
A5	Placebo Placebo	lifestyle: standard	77	77	46

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Survodutide 0.6 mg subcutaneous once weekly A1	Survodutide 2.4 mg subcutaneous once weekly A2	Survodutide 3.6 mg subcutaneous once weekly A3	Survodutide 4.8 mg subcutaneous once weekly A4	Placebo A5	Whole trial ALL
age	mean (years)	48.6	49.0	50.3	47.6	50.0
age	sd (years)	12.6	13.1	11.8	13.5	13.5
asian	n	8	9	9	7	7
black	n	10	8	3	8	8
bmi: 30 to less than 35	n						117
bmi: 30 to less than 35	percent						30.5
bmi: 35 to less than 40	n						122
bmi: 35 to less than 40	percent						31.8
bmi: 40 or more	n						107
bmi: 40 or more	percent						27.9
bmi: less than 30	n						38
bmi: less than 30	percent						9.9
female	n	51	54	51	53	53
hispanic	n	3	1	2	6	5
other race american indian alaska native	n	0	0	0	1	0
other race multiple	n	0	1	1	0	1
other race native hawaiian pacific islander	n	0	0	0	1	1
weight	mean (kg)	106.98	106.57	104.68	105.86	104.32
weight	sd (kg)	18.71	22.97	19.63	17.39	22.95
white	n	59	60	63	59	60

Analyses this trial contributes to

Results

131 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

Systolic blood pressure change (9 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
46	A1	change	-6.19 mmHg	1.47		75	while on treatment; full analysis; registry:outcomes
46	A1 vs A5	md	-3.73 mmHg	2.08	-7.82 to 0.35		while on treatment; full analysis; registry:outcomes
46	A2	change	-8.08 mmHg	1.48		78	while on treatment; full analysis; registry:outcomes
46	A2 vs A5	md	-5.62 mmHg	2.08	-9.71 to 1.53		while on treatment; full analysis; registry:outcomes
46	A3	change	-8.66 mmHg	1.44		76	while on treatment; full analysis; registry:outcomes
46	A3 vs A5	md	-6.20 mmHg	2.05	-10.23 to -2.17		while on treatment; full analysis; registry:outcomes
46	A4	change	-8.62 mmHg	1.46		76	while on treatment; full analysis; registry:outcomes
46	A4 vs A5	md	-6.16 mmHg	2.08	-10.25 to -2.06		while on treatment; full analysis; registry:outcomes
46	A5	change	-2.46 mmHg	1.46		76	while on treatment; full analysis; registry:outcomes

Percent body weight change (21 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
46	A1	percent change	-6.19 percent	1.07		76	treatment policy; full analysis; registry:outcomes
46	A1 vs A5	md	-3.37 percent	1.50	-6.33 to -0.41		treatment policy; full analysis; registry:outcomes
46	A2	percent change	-12.51 percent	1.01		78	treatment policy; full analysis; registry:outcomes
46	A2 vs A5	md	-9.69 percent	1.46	-12.57 to -6.81		treatment policy; full analysis; registry:outcomes
46	A3	percent change	-13.22 percent	1.04		76	treatment policy; full analysis; registry:outcomes
46	A3 vs A5	md	-10.40 percent	1.48	-13.32 to -7.49		treatment policy; full analysis; registry:outcomes
46	A4	percent change	-14.94 percent	1.01		76	treatment policy; full analysis; registry:outcomes
46	A4 vs A5	md	-12.12 percent	1.46	-15.00 to -9.24		treatment policy; full analysis; registry:outcomes
46	A4	percent change	-15.8 percent				treatment policy; full analysis; bmi:30_to_less_than_35; R0015637:Abstract
46	A4	percent change	-15.4 percent				treatment policy; full analysis; bmi:35_to_less_than_40; R0015637:Abstract
46	A4	percent change	-13.4 percent				treatment policy; full analysis; bmi:40_or_more; R0015637:Abstract
46	A4	percent change	-19.1 percent				treatment policy; full analysis; bmi:less_than_30; R0015637:Abstract
46	A4	percent change	-17.0 percent				treatment policy; full analysis; sex:female; R0015235:Results
46	A4	percent change	-11.9 percent				treatment policy; full analysis; sex:male; R0015235:Results
46	A5	percent change	-0.8 percent				treatment policy; full analysis; bmi:40_or_more; R0015637:Abstract
46	A5	percent change	-2.82 percent	1.06		77	treatment policy; full analysis; registry:outcomes
46	A5	percent change	-3.2 percent				treatment policy; full analysis; sex:female; R0015235:Results
46	A5	percent change	-3.1 percent				treatment policy; full analysis; bmi:30_to_less_than_35; R0015637:Abstract
46	A5	percent change	-1.7 percent				treatment policy; full analysis; bmi:less_than_30; R0015637:Abstract
46	A5	percent change	-5.8 percent				treatment policy; full analysis; bmi:35_to_less_than_40; R0015637:Abstract
46	A5	percent change	-3.3 percent				treatment policy; full analysis; sex:male; R0015235:Results

Weight loss of 5 percent or more (9 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
46	A1 vs A5	or	3.28	1.57 to 6.84		treatment policy; full analysis; registry:outcomes
46	A1	responders	60.7		56	treatment policy; full analysis; registry:outcomes
46	A2	responders	81.0		58	treatment policy; full analysis; registry:outcomes
46	A2 vs A5	or	8.83	4.00 to 19.46		treatment policy; full analysis; registry:outcomes
46	A3	responders	82.0		61	treatment policy; full analysis; registry:outcomes
46	A3 vs A5	or	7.48	3.41 to 16.41		treatment policy; full analysis; registry:outcomes
46	A4	responders	82.8		64	treatment policy; full analysis; registry:outcomes
46	A4 vs A5	or	10.77	4.77 to 24.31		treatment policy; full analysis; registry:outcomes
46	A5	responders	25.9		54	treatment policy; full analysis; registry:outcomes

Weight loss of 10 percent or more (9 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
46	A1	responders	33.9		56	treatment policy; full analysis; registry:outcomes
46	A1 vs A5	or	3.22	1.29 to 8.02		treatment policy; full analysis; registry:outcomes
46	A2	responders	65.5		58	treatment policy; full analysis; registry:outcomes
46	A2 vs A5	or	10.62	4.36 to 25.86		treatment policy; full analysis; registry:outcomes
46	A3	responders	65.6		61	treatment policy; full analysis; registry:outcomes
46	A3 vs A5	or	9.78	4.02 to 23.79		treatment policy; full analysis; registry:outcomes
46	A4	responders	68.8		64	treatment policy; full analysis; registry:outcomes
46	A4 vs A5	or	14.50	5.91 to 35.55		treatment policy; full analysis; registry:outcomes
46	A5	responders	11.1		54	treatment policy; full analysis; registry:outcomes

Weight loss of 15 percent or more (9 lines; O11C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
46	A1 vs A5	or	2.13	0.56 to 8.02		treatment policy; full analysis; registry:outcomes
46	A1	responders	12.5		56	treatment policy; full analysis; registry:outcomes
46	A2	responders	37.9		58	treatment policy; full analysis; registry:outcomes
46	A2 vs A5	or	9.47	2.89 to 30.95		treatment policy; full analysis; registry:outcomes
46	A3	responders	45.9		61	treatment policy; full analysis; registry:outcomes
46	A3 vs A5	or	11.79	3.62 to 38.36		treatment policy; full analysis; registry:outcomes
46	A4 vs A5	or	21.02	6.47 to 68.28		treatment policy; full analysis; registry:outcomes
46	A4	responders	54.7		64	treatment policy; full analysis; registry:outcomes
46	A5	responders	5.6		54	treatment policy; full analysis; registry:outcomes

All cause mortality (9 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 77	while on treatment; safety; registry:adverse_events
A1	events	0 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	0 / 78	while on treatment; safety; registry:adverse_events
A2	events	0 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	0 / 77	while on treatment; safety; registry:adverse_events
A3	events	0 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	0 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A4	events	0 / 77	while on treatment; safety; registry:adverse_events
A5	events	0 / 77	while on treatment; safety; registry:adverse_events

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	2 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	3 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	4 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	4 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A5	events	5 / 77	while on treatment; safety; registry:adverse_events

Discontinuation due to adverse events (20 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	2 / 55	not stated; randomized; adverse event; registry:flow
A1	events	4 / 78	not stated; randomized; adverse event: covid-infection; registry:flow
A1	events	9 / 78	not stated; randomized; adverse event; registry:flow
A1	events	0 / 55	not stated; randomized; adverse event: covid infection; registry:flow
A2	events	10 / 78	not stated; randomized; adverse event; registry:flow
A2	events	8 / 60	not stated; randomized; adverse event; registry:flow
A2	events	1 / 78	not stated; randomized; adverse event: covid-infection; registry:flow
A2	events	1 / 60	not stated; randomized; adverse event: covid infection; registry:flow
A3	events	5 / 59	not stated; randomized; adverse event; registry:flow
A3	events	0 / 59	not stated; randomized; adverse event: covid infection; registry:flow
A3	events	12 / 77	not stated; randomized; adverse event; registry:flow
A3	events	2 / 77	not stated; randomized; adverse event: covid-infection; registry:flow
A4	events	17 / 77	not stated; randomized; adverse event; registry:flow
A4	events	1 / 77	not stated; randomized; adverse event: covid-infection; registry:flow
A4	events	0 / 55	not stated; randomized; adverse event: covid infection; registry:flow
A4	events	4 / 55	not stated; randomized; adverse event; registry:flow
A5	events	0 / 57	not stated; randomized; adverse event: covid infection; registry:flow
A5	events	1 / 57	not stated; randomized; adverse event; registry:flow
A5	events	3 / 77	not stated; randomized; adverse event; registry:flow
A5	events	0 / 77	not stated; randomized; adverse event: covid-infection; registry:flow

Nausea (10 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A1	events	36 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	60 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A2	events	0 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	0 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A3	events	45 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	32 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A4	events	0 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A5	events	0 / 77	while on treatment; safety; registry:adverse_events
A5	events	15 / 77	while on treatment; safety; registry:adverse_events

Vomiting (10 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A1	events	13 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	28 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A2	events	0 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	28 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A3	events	0 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	0 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A4	events	13 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A5	events	0 / 77	while on treatment; safety; registry:adverse_events
A5	events	4 / 77	while on treatment; safety; registry:adverse_events

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	22 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	21 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	17 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	9 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A5	events	8 / 77	while on treatment; safety; registry:adverse_events

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	11 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; registry:adverse_events
A2	events	19 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; registry:adverse_events
A3	events	22 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; registry:adverse_events
A4	events	13 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; registry:adverse_events
A5	events	4 / 77	while on treatment; safety; registry:adverse_events

Gallbladder and biliary disease (10 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; cholecystitis; registry:adverse_events
A1	events	0 / 92	while on treatment; safety; group:actual_maintenance_0p6_mg; cholelithiasis; registry:adverse_events
A2	events	0 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; cholelithiasis; registry:adverse_events
A2	events	0 / 92	while on treatment; safety; group:actual_maintenance_2p4_mg; cholecystitis; registry:adverse_events
A3	events	0 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; cholelithiasis; registry:adverse_events
A3	events	0 / 71	while on treatment; safety; group:actual_maintenance_3p6_mg; cholecystitis; registry:adverse_events
A4	events	1 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; cholelithiasis; registry:adverse_events
A4	events	1 / 54	while on treatment; safety; group:actual_maintenance_4p8_mg; cholecystitis; registry:adverse_events
A5	events	0 / 77	while on treatment; safety; cholecystitis; registry:adverse_events
A5	events	0 / 77	while on treatment; safety; cholelithiasis; registry:adverse_events